tbuckley/cabot-search huggingface dataset:
P08.09.A Improving support for family carers: Creating a cross-sector collaborative working group
Authors: E Nicklin, J Jopson, F Boele
Journal: Neuro-Oncology (2022)

Abstract Background Family carers of people with brain tumours and other progressive neurological conditions have unique but overlapping support needs. This is because caring can be particularly challenging due to patients’ cognitive issues, behavioural changes, and neuropsychiatric symptoms. We undertook stakeholder engagement work to bring together family carers, academics, service providers and policy makers to form a working group and highlight opportunities for improvement of family carer (FC) support. Material and Methods Sixteen stakeholders (academics, carers, charity representatives, clinicians and policy makers) participated in two one-hour online workshops (N=8 in each). Workshops started with introductions, an outline of meeting objectives, and a specially created animated video introducing the topic. A structured discussion followed, focusing on current FC support and barriers in accessing support. Finally, we covered blue-sky thinking exercises, with attendees describing their ideal vision of FC support in the future; and how the group can work together to improve support. Workshop findings were integrated into a position statement. Results The position statement covers five pillars for joint action. 1) Collaboration, coordination, and co-design - current support is fragmented. Better collaboration is needed between the social care sector, the third sector, and healthcare systems, to stop struggling FCs falling through the net. 2) Valuing carers - there is a need to acknowledge and enhance the awareness of FC contributions, e.g. through co-producing research publications highlighting the value FCs bring. 3) Redefine personalised medicine- carer support needs are varied and no one size fits all. Personalised care is key to identify specific needs of carers arising from aspects of diversity, such as ethnicity and age. 4) Flexible evidence-based support- we need to build a better evidence-base for FC support; and prioritise evidence-based support. This is especially important given the scarcity of funds and resources for FCs. 5) Promotion of current support services- many FCs do not know where to get support locally. More research can help to identify barriers and facilitators to support carers’ access to formal support. Conclusion: To improve support for FCs, we need to move away from fragmented approaches and move towards a more collaborative approach with carers at the centre. Our collective vision is that future support is based on what matters to them as individuals and what is effective in meeting their needs. We strive to provide flexible, accessible, responsive and inclusive support for FCs, and invite other carers, service providers, academics and policymakers to join our effort.
P11.74.A Plexiform Neurofibromas prevalence and treatment modalities in a referral comprehensive cancer center
Authors: M Ferreira, J Costa, D Antão, E Silva, J Passos, M Vilares, H Vasques, I Patrocínio, C Silva, F Santos, D Salgado, M Lacerda
Journal: Neuro-Oncology (2022)

Abstract Background Neurofibromatosis type 1 (NF1) is the most common tumor predisposition syndrome, with an incidence of 1/3500. Plexiform neurofibromas (PN) are benign tumors that can occur along the nerve sheath throughout the body, with unpredictable growth and with risk of malignant transformation. Symptoms will depend on their size and location, and include pain, deformity and functional impairment. There is a great variability in the PN severity and impact on quality-of-life (QOL). An unknown percentage of NF1 patients may need treatment, either medical and/or surgical. Objectives To assess the frequency of PN in a NF1 population followed in a comprehensive cancer center. Material and Methods Retrospective study. All patients with NF1 and PN followed in our center, between 31/12/2000 and 31/12/2021. Results Of 438 NF1 patients, 185 had PN (42%). 52 NF1 patients with PN were children (≤ 18). The most common symptoms were pain in 71 people (38,4%), deformity in 70 (37,8%) and functional impairment in 69 (37,3%). Several patients had a combination of these symptoms. Different treatment modalities were used for PN: medical, surgical or both. In this study, 54 patients (29,1%) were treated with MEK inhibitors (selumetinib), 74 patients (40%) were treated surgically and 12,4% (23) needed a combined approach (medical and surgical treatment). Conclusion PN are frequent in NF1 patients. A significant percentage is symptomatic and will require treatment, surgical, medical or both. There is no standard of care for PN NF1. The timing and sequence of medical and surgical treatment is yet to be defined.
P18.10.B Natural history of meningiomas - a serial volumetric analysis of 240 tumors
Authors: P Thomann, L Häni, S Vulcu, A Schütz, M Frosch, C M Jesse, M El-Koussy, N Söll, A Hakim, A Raabe, P Schucht
Journal: Neuro-Oncology (2022)

Abstract Background The management of asymptomatic intracranial meningiomas is controversial. Through the assessment of growth predictors, we aimed to create the basis for practicable clinical pathways for the management of these tumors. Material and Methods We volumetrically analyzed meningiomas radiologically diagnosed at our institution between 2003 and 2015. For this purpose, we used exclusively thin-layered MR images (i.e. ≤ 2mm slice thickness). The primary endpoint was tumor growth defined as a 14.35% increase in tumor volume. We identified predictive clinical and radiological characteristics and used the significant variables from a multivariable regression model to construct a decision tree based on the exhaustive Chi-squared Automatic Interaction Detection (exhaustive CHAID) algorithm. Results Of 240 meningiomas, 159 (66.3%) demonstrated growth during a mean observation period of 46.9 months. On multivariable logistic regression analysis, older age (OR=0.979 (0.958-1.000), p=0.048) and presence of calcification (OR=0.442 (0.224-0.872), p=0.019) had a negative predictive value for tumor growth, while T2-signal iso-/hyperintensity (OR=4.415 (2.056-9.479), p&amp;lt;0.001) had a positive predictive value. A decision tree model yielded three growth risk groups based on T2-signal intensity and presence of calcifications with a proportion of growing tumors of 34.1% in the low risk group, 60.0% in the intermediate risk group and 80.2% in the high risk group. Median tumor volume doubling time (Td) was 185.7 months in the low risk, 100.1 months in the intermediate risk and 51.7 months in the high risk group (p&amp;lt;0.001). While 0% of meningiomas in the low and intermediate risk group had a Td of ≤12 months, 8.9% in the high risk group did so (p=0.021). Conclusion Most meningiomas demonstrated growth during follow-up. The presence or absence of calcifications and the signal intensity on T2-weighted imaging allow a practical and simple stratification of meningiomas into low, intermediate and high risk tumors. Small tumors in the low or intermediate risk categories can be monitored with longer follow-up intervals, whereas in the high risk category proactive management decisions can be justified.
P11.50.A Surgical results and long-term outcome in supratentorial intraventricular tumors
Authors: N Teske, M Chiquillo, B Skrap, J Blobner, L von Baumgarten, M Kunz, J Tonn, N Thon, P Karschnia
Journal: Neuro-Oncology (2022)

Abstract Background Intraventricular tumors (IVTs) are rare lesions of various entities, which pose a surgical challenge. We aimed to elaborate on surgical approaches and outcomes, postoperative morbidity, and elucidate whether preoperative hydrocephalus necessitates shunting despite surgical resection. Material and Methods We retrospectively searched the institutional database for patients with supratentorial intraventricular tumours that were treated in the Department of Neurosurgery of the Ludwig-Maximilians-University Munich, Germany between 2014 and 2022. Results We identified 60 patients with supratentorial intraventricular tumors comprising over 10 different tumor entities, most often subependymoma (8/60 patients, 13.4%). Median age at diagnosis was 45.5 ± 3.0 years with 31 male patients (51.6%) and 29 female patients (48.3%). Microsurgical tumor resection was completed in 44 patients (45/60 patients, 75%; gross total resection: 36/45 patients, 80%; subtotal resection: 9/45 patients, 20%). In cases where neurosurgical tumor resection was not feasible, stereotactic biopsy was provided in 15/60 patients (25%), often combined with stereotactic internal shunt implantation (8/60 patients, 13.3%). Mean follow-up was 17 months; median overall survival was not reached. Postoperative persistent hydrocephalus necessitating ventriculoperitoneal shunt placement was rare (4/60 patients, 6.7%). Ventriculocisternostomy was performed in one patient. New postoperative focal neurological deficits - mostly transient - were encountered in 16/60 patients (26.6%) at discharge. Postoperative adverse events rate was 11.7%. Conclusion Complete resection of IVT can often be achieved and forms the basis for favourable outcome. Permanent neurological deficits are rare, and hydrocephalus can almost always be alleviated which prevents the need for long-term shunting. If microsurgical resection is not feasible, stereotactic biopsy along with internal shunting represents an effective approach to establish diagnosis and ameliorate symptoms.
P11.42.A Short course of Bevacizumab for differential diagnosis of tumor progression and radionecrosis or pseudoprogression after brain metastasis SRS
Authors: K Nikitin
Journal: Neuro-Oncology (2022)

Abstract Background Despite use of modern MRI techniques (perfusion, spectroscopy, TRAMs, radiomics), PET and SPECT the differential diagnosis of radio-necrosis and tumor progression is still difficult in malignant gliomas and brain metastasis after radiotherapy or radiosurgery. For patients who have enlargement of brain metastasis after radiosurgery we suggest a new strategy to discriminate pseudoprogression and true progression - two intravenous infusions Bevacizumab in 5-7 mg/kg with 2-3 week interval and new contrast MR. Material and Methods We present 3 relevant clinical cases, all after LINAC-based SRS for brain metastasis.1st case - 49 y.o. female with ovarian cancer underwent SRS for two small closely seated metastases in temporal lobe, both metastasis had shrunk and remained stable until 34 months after radiosurgery a new asymptomatic contrasting lesion with edema developed on MRI adjacent to one of metastasis. Patient developed no other new brain or extracranial mets, so we proposed radionecrosis, but MR-perfusion data was ambiguous. 2nd case - 67 y.o. female with lung adenocarcinoma underwent SRS (27 Gy in 3 fractions) for solitary brain metastasis. 4 months after SRS metastasis partially regressed, but 4 months later a new contrast enhancement zone appeared on its periphery with edema. 18F-FET PET failed to differentiate recurrence and pseudoprogression. 3d case - 48 y.o. female with breast cancer underwent SRS (27 Gy in 3 fractions) for 3 brain metastases. All mets regressed during the next 7 months, but 3 months later one of them showed significant symptomatic enlargement with edema on MRI. All patients received two intravenous infusions Bevacizumab in 5-7 mg/kg with 2-3 week interval and new contrast MRI (1-2 week after second infusion). Results 1st case - after two infusions of 6 mg/kg with a 3-week interval new contrasting zone disappeared and did not develop again for at least 6 months (with no chemotherapy), so we confirmed necrosis. 2nd case - substantial regression of pathological MRI changes was noted, which was stable for 3 months, diagnostic for pseudoprogression. 3d case - MRI showed substantial regress of contrasting lesion (diagnostic for necrosis), symptoms also regressed and 1 month later methionine PET showed no active tumor. Conclusion Our preliminary data suggest that use of two infusions of Bevacizumab and routine contrast MRI have very promising diagnostic value to rule out tumor growth after SRS of brain metastasis.
P11.04.A Observational, prospective multicenter study on the role of body mass index (BMI) in the development of thrombotic complications in cancer patients with PICC: preliminary results
Authors: G Simonetti, M Gammone, A Bersani, R Garofalo, E Anghileri, A Botturi, P Gaviani, V Redaelli, A Silvani
Journal: Neuro-Oncology (2022)

Abstract Background Peripherally inserted central catheters (PICC) became widespread and changed substantially the approach to the patients venous system. They guarantee, both in hospital and at home, a stable and safe vascular access to administer irritants or vesicants therapies. However, the benefit provided may occasionally be affected by relevant thrombotic complications especially in patients with hypercoagulability such as oncological patients. Among the identification of independent risk factors, the role of a BMI&amp;gt;25 kg/m2 is now emerging in literature with conflicting results. Material and Methods Oncological patients with PICC were included in this multicenter prospective study. We evaluated clinical data, BMI, KPS, steroid therapies and anticoagulants at the time of PICC positioning and at regular intervals. Results A total of 51 patients were analyzed. The median KPS was 90 (range 80-100), and the median ECOG was 1 (range 0-3). The most common tumors were represented by: lymphomas both Hodgkin and non-Hodgkin (38%), lymphatic and myeloid leukemia (35%), neurooncological tumors including glioblastoma, primary central nervous system lymphoma, anaplastic astrocytoma and meningioma (15%), other solid cancer (breast, gastroesophageal, rectal cancer) (12%).55% patients were at first diagnoses, 12% were at the first recurrence, and the remaining were at the second or third recurrence. No malpositioning were registered. 18% of patients were on anticoagulant/antiplatelet therapy, 67% were treated with steroids. Concerning BMI, 39% was normal weight, 43% overweight and 10% obese, only 2% was considered underweight. Overall, 8% of patients developed PICC related thrombosis within a median time of 68 days (49-87) after PICC implantation mainly occurred in upper right extremity insertion sites. We therefore assessed the incidence of PICC related thromboembolic events in the groups, with 4% of event registered in the cohort of patients overweight/obese, and 14% of events in the cohort of patients with normal weight/underweight. Conclusion Preliminary analysis does not allow to draw firm conclusions. It will therefore be necessary to reach the sample size for achieve generalizable results and confirm the risk of developing thromboembolic events in overweight/obese patients. Meanwhile, an accurate anamnesis and a physical evaluation with particular attention to the presence of malnutrition, both over nutrition and undernutrition, could help to identify potential oncological patients at risk of developing PICC related thrombosis.
JS04.5.A Enhancing the activity of anti-CD47 antibody therapy with radiotherapy in preclinical models of medulloblastoma
Authors: Z Abbas, M Howlett, J Buck, H Hii, M Kuchibhotla, M Ancliffe, J Whitehouse, T Johns, M Ebert, N Gottardo, R Endersby
Journal: Neuro-Oncology (2022)

Abstract Background Brain cancers are the most common solid cancer in children and the leading cause of cancer-related deaths in children. Medulloblastoma is the most common paediatric brain tumour. Treatment for medulloblastoma involves surgery, craniospinal irradiation (CSI) and chemotherapy. These therapies are extremely damaging to the developing brain and have not changed in decades, resulting in stagnation in the survival outcomes for children with medulloblastoma, and poor quality of life for children who survive their treatment. Immunotherapy has become a focus of novel treatment development. While there are multiple clinical trials aiming to increase immune recognition of medulloblastoma, none have been successful to date. Anti-CD47 is an immune-modulating therapeutic antibody which blocks the anti-phagocytic signal, CD47, expressed by brain cancer cells. Anti-CD47 has shown promising preliminary efficacy in brain cancer models. Material and Methods Using a small animal radiotherapy platform, we have developed a preclinical CSI protocol which mimics clinical radiotherapy. Using an orthotopic xenograft model of medulloblastoma, mice were treated with either anti-CD47 antibody therapy, CSI, or the combination of both anti-CD47 and CSI. Results CSI was found to deplete adaptive immune cells in the brain, while myeloid cells remained the dominant populations. Anti-CD47 antibody therapy was ineffective as a single agent against a patient derived xenograft model of Group 3 medulloblastoma, and CSI as a monotherapy resulted in temporary tumour regression. We found that the combination of anti-CD47 with CSI resulted in marked and persistent tumour regression. Conclusion This preclinical work has shown promising efficacy of anti-CD47 in combination with CSI, which we are currently testing in additional models. Our work is currently employing a range of techniques such as high dimensional flow cytometry and single cell sequencing to elucidate the mechanisms by which radiotherapy enhances the anti-tumour activity of myeloid cells. This work will enable the rational design and translation of optimal combination therapies for medulloblastoma clinical trials.
P17.02.A IPAX-1: phase 1/2 study of131I-iodo-phenylalanine (131IIPA) combined with external radiation therapy as treatment for patients with relapsed glioblastoma
Authors: J Pichler, A Leibetseder, I Höllmüller, T Traub-Weidinger, F Fitz, H Geinitz, J Feichtinger, T Brown, C Hayward
Journal: Neuro-Oncology (2022)

Abstract Background A novel therapeutic approach using molecularly targeted radiation is currently in development for patients with recurrent GBM. Many tumor types, including GBM, overexpress the L-type amino transporter 1 (LAT-1)4, which is able to internalize the small-molecule amino acid derivative, 4-L-[131I] iodo-phenylalanine (131I-IPA). In preclinical research, combining 131I-IPA with external radiation therapy (XRT) yielded additive cytotoxic effects. Tumoral accumulation of 131I-IPA was confirmed in a proof-of-principle study using single doses of 2-7 GBq 131I-IPA as a monotherapy or in combination with XRT in patients with recurrent GBM. The objective of the IPAX-1 study was to evaluate the safety, tolerability, dosing schedule, and preliminary efficacy of 131I-IPA in combination with second-line radiotherapy in patients with recurrent GBM. Methods IPAX-1 is a multi-center, open-label, single-arm, dose-finding phase 1/2 study. Key inclusion criteria: 1. Confirmed histological diagnosis of GBM with evidence of first recurrence 2. History of GBM standard therapy 3. ≥ 6 months since end of first-line XRT 4. Pathologically increased amino acid tumor uptake shown by molecular imaging 5. Current indication for repeat radiation 6. Gross tumour volume of up to 4.8 cm diameter. Treatment: In phase 1 of the study patients received intravenous 131I-IPA at a dose level of 2 GBq administered in one of three different dosing regimens: single dose group with 2 GBq before radiation, 3 (f)-fractionated-parallel group: 3 x 0.67 GBq during XRT and 3 (f)-fractionated-sequential group: 0.67 GBq x 1 → XRT → 0.67 GBq x 2. XRT is delivered in 18 fractions of 2 Gy each. Results 10 patients were randomized; one patient with Covid related death was withdrawn from analysis. Survival from start of TLX101 therapy showed mPFS2 of 4.33 M (95% -CI 4.18 - 4.48), PFS-6: 18 % and mOS2 of 15.97 M (95% -CI 2.9 - 29.1) at data lock 09/2021. Updated results will be presented at the meeting. Conclusion There were no clinically relevant laboratory changes over time. Urinalysis, vital signs, and ECG did not show any clinically relevant changes from baseline. There were no notable differences in safety and tolerability between groups. Injections of single or fractionated doses of 131I-IPA containing a total activity of 2 GBq in combination with XRT in patients with recurrent GBM were safe and well tolerated. Survival data look promising; extension cohort will be treated in a phase II study in Linz; phase 1/2 study in first line setting is planned.
P10.03.B Insights into the development of tunable brain implants for local chemotherapy
Authors: L Waldherr, V Handl, T Abrahamsson, T Arbring Sjöström, M Seitanidou, S Erschen, S Honeder, T Tomin, R Birner-Grünberger, N Ghaffari Tabrizi-Wizsy, S Ropele, M Ücal, M Nowakowska, U Schäfer, S Patz, D Simon, R Schindl
Journal: Neuro-Oncology (2022)

Abstract Background Glioblastomas (GBMs) remain an unmastered medical challenge. Poor delivery and systemic toxicity of many chemotherapeutic agents limit their therapeutic success in GBM treatment. Bioelectronic implants for local chemo drug delivery can optimize drug concentrations at the tumor site, duration of treatment and tumor suppression, while systemic effects remain at an acceptable low level. We present miniature bioelectronic devices for drug delivery able to administer chemotherapeutics via electric control with high spatiotemporal precision.1 The drug delivery is based on the electro migration of drug molecules in an ion selective matrix towards a target of choice. These bioelectronic devices, called chemotherapeutic ion pumps (chemoIPs), can be used for triggered drug release of chemotherapeutics that are usually shielded by the blood brain barrier. Material and Methods The performance of chemoIPs is studied in different brain tumor models with increasing complexity (cell culture and different in vivo models). With chemoIPs it is possible to constantly administer drugs with highest precision (delivery rates at pmol*min-1 precision) towards cell culture spheroids, ex ovo-grown tumors and in vivo brain tumors Results The treatment efficiency was analyzed via flow cytometry quantifying apoptosis and cell cycle arrest, as well as immune-histochemical analysis for apoptosis. ChemoIP treatment is able to trigger the disintegration of targeted tumor spheroids, and is able to inhibit the tumor growth of ex ovo-grown glioblastomas significantly. Furthermore, the proteomes of neurons and glioblastoma cells were recorded via proteomics, which showed that only GBM cells are harmed by the chemotherapeutic treatment, but not neurons. In parallel, can follow the pharmacokinetics of the chemoIP-mediated drug administration via drug quantification using mass spectrometry and compare it to computer simulations in different tumor models. Conclusion The here exemplified electrically-driven drug delivery via chemoIPs is a drug administration method that can serve as basis for further implant development, which has the potential to increase the efficacy of chemotherapy due to highly-targeted and locally-controlled drug delivery.